title: OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation.
abstract: Macroautophagy is a bulk degradation system conserved in all eukaryotic cells. A ubiquitin-like protein, Atg8, and its homologues are essential for autophagosome formation and act as a landmark for selective autophagy of aggregated proteins and damaged organelles. In this study, we report evidence demonstrating that OATL1, a putative Rab guanosine triphosphatase-activating protein (GAP), is a novel binding partner of Atg8 homologues in mammalian cells. OATL1 is recruited to isolation membranes and autophagosomes through direct interaction with Atg8 homologues and is involved in the fusion between autophagosomes and lysosomes through its GAP activity. We further provide evidence that Rab33B, an Atg16L1-binding protein, is a target substrate of OATL1 and is involved in the fusion between autophagosomes and lysosomes, the same as OATL1. Because both its GAP activity and its Atg8 homologue-binding activity are required for OATL1 to function, we propose a model that OATL1 uses Atg8 homologues as a scaffold to exert its GAP activity and to regulate autophagosomal maturation.
authors.affiliation: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Itoh
authors.forename: Eiko
authors.initials: E
authors.lastname: Kanno
authors.forename: Takefumi
authors.initials: T
authors.lastname: Uemura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Waguri
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071190:Autophagy-Related Protein 8 Family; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000502:physiology; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism; D008969:Molecular Sequence Data; D025941:Protein Interaction Mapping; D011993:Recombinant Fusion Proteins / Q000032:analysis; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071190:Autophagy-Related Protein 8 Family; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C480861:GABARAP protein, mouse; D020690:GTPase-Activating Proteins; C407740:Gabarapl2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C480860:Map1lc3b protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C559092:OATL1 protein, mouse; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C112838:Rab33B protein, mouse; D020691:rab GTP-Binding Proteins